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ET9A2841

Phagocytes, NADPH oxydases et immunogénétique dans l’inflammation systémique

Team El Benna

Department Nephrology, Immunology and Hematology

 

Team leader

 

Line-up

Team leader

 

Presentation

Our team is interested in studying molecular and cellular mechanisms of inflammation, focusing on the regulationof the main reactive oxygen species (ROS) producing enzymes, the NADPH oxidases (NOXs) and their role in thephysiopathology of inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel diseases (IBD). When their production is controlled, reactive oxygen species (ROS) are involved in many important physiological functions. Thus ROS produced by the phagocyte NADPH oxidase, NOX2, in neutrophils, monocytes and macrophages are required for their bactericidal function, and importantly in dendritic cells, NOX2 has a critical role in antigen cross-presentation. Homologues of NOX2, such as NOX1, are also expressed in epithelial cells, but their physiological role is not fully understood. On the other hand, it is clear that excessive or inappropriate ROS production can induce severe tissue injury that participates to the physiopathology of inflammatory diseases. Deciphering mechanisms underlying activation of NOX2 in phagocytes and NOX1 in epithelial cells is essential to identify novel therapeutic targets in inflammation. The projects of the team aim to understand the regulation of NOX2 in neutrophils, monocytes/macrophages and dendritic cells and NOX1 in epithelial cells by pro- and anti-inflammatory agents; and to translate our basic research to animal models of inflammation, human phagocytic disorders and human inflammatory diseases. Our project combines basic and clinical research and involves several collaborations with teams in the Center for Research on Inflammation (CRI) and Bichat hospital divisions.

Principal research axis:

Our work is conducted following three main axis : 1)-To understand the regulation of the NADPH oxidases NOX in neutrophils, monocytes, macrophages, dendritic cells and epithelial cells in response to pro- and anti-inflammatory agents. 2)-To study polymorphism of NOX and regulators and identify new genetic factors involved in systemic inflammation. 3-To study the role of the NOX2, NOX1 and newly identified proteins in inflammatory process: by investigating their activation in phagocytic disorders, human inflammatory diseases and in animal models of inflammation.

 

Landmark publications

  • Publication date : 01 July 2020 More

    Innate immune cells in cirrhosis J Hepatol

    Autors : Christine Bernsmeier Schalk van der Merwe Perianin Axel

  • Publication date : 22 January 2020 More

    The dual role of ROS-generating NADPH oxidases in gastrointestinal inflammation and therapeutic perspectives. Antioxidants & Redox Signaling. 2020 Jan 22

    Autors : Dang Pham My-Chan Rolas L El Benna Jamel

  • Publication date : 01 November 2019 More

    The prolyl isomerase Pin1 controls lipopolysaccharide-induced priming of NADPH oxidase in human neutrophils. Frontiers In Immunology Frontiers In Immunology (sous presse).

    Autors : Liu Min Bedouhene Samia Hurtado-Nedelec Maria Margarita Pintard Coralie Dang Pham My-Chan Yu S El Benna Jamel

  • Publication date : 06 September 2019 More

    Cytosolic PCNA interacts with p47phox and controls NADPH oxidase NOX2 activation in neutrophils. J Exp Med. 2019 Sep 6. pii: jem.20180371.

    Autors : Ohayon D De Chiara A Dang Pham My-Chan Thieblemont N Chatfield S Marzaioli V Burgener SS Mocek J Candalh C Pintard Coralie Tacnet-Delorme P Renault G Lagoutte I Favier M Walker Francine Hurtado-Nedelec Maria Margarita Desplancq D Weiss Emmanuel Benarafa C Housset D Marie Jean-Claude Frachet P El Benna Jamel Witko-Sarsat V

  • Publication date : 01 March 2019 More

    The Kinesin Light Chain-Related Protein PAT1 Promotes Superoxide Anion Production in Human Phagocytes. J Immunol. 2019 Mar 1;202(5):1549-1558

    Autors : Arabi-Derkawi R O'Dowd Y Cheng N Rolas L Boussetta T Raad H Marzaioli V Pintard Coralie Fasseu M Kroviarski Y Belambri SA Dang Pham My-Chan Ye RD Gougerot-Pocidalo Marie-Anne El Benna Jamel

  • Publication date : 02 October 2018 More

    NOX1-derived ROS drive the expression of Lipocalin-2 in colonic epithelial cells in inflammatory conditions Mucosal Immunology, 2018 Oct doi: 10.1038/s41385-018-0086-4.

    Autors : Makhezer N Ben-Khemis Marwah Liu Dan Khichane Y Marzaioli V Tlili A Mojallali Marjan Pintard Coralie Letteron Philippe Hurtado-Nedelec Maria Margarita El Benna Jamel Marie Jean-Claude Sannier A Pelletier Anne-Laure Dang Pham My-Chan

  • Publication date : 09 July 2018 More

    NADPH oxidase depletion in neutrophils from patients with cirrhosis and restoration via toll-like receptor 7/8 activation Gut. 2018;67(8):1505-1516

    Autors : Rolas L Boussif A Weiss Emmanuel Letteron Philippe Haddad O El Benna Jamel Rautou Pierre-Emmanuel Moreau Richard Perianin Axel

  • Publication date : 12 October 2017 More

    NOX5 and p22phox are 2 novel regulators of human monocytic differentiation into dendritic cells. Blood. 2017 Oct 12;130(15):1734-1745

    Autors : Marzaioli V Hurtado-Nedelec Maria Margarita Pintard Coralie Tlili A Marie Jean-Claude Monteiro RC Gougerot-Pocidalo Marie-Anne Dang Pham My-Chan El Benna Jamel

  • Publication date : 01 March 2017 More

    Vasoactive intestinal peptide dampens formyl-peptide-induced ROS production and inflammation by targeting a MAPK-p47(phox) phosphorylation pathway in monocytes Mucosal Immunology, 2017 Mar;10(2):332-340

    Autors : Chedid P Boussetta T Dang Pham My-Chan Belambri SA Marzaioli V, Fasseau M Walker Francine Couvineau Alain El Benna Jamel Marie Jean-Claude

 
 

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Latest Publications

  • Publication date : 30 December 2020 More

    Mast Cell Chymase and Kidney Disease International Journal of Molecular Sciences

    Autors : Vibhushan Shamila Bratti Manuela Juan Eduardo Montero-Hernández Alaa El Ghoneimi Benhamou Marc Charles Nicolas Daugas Eric Blank Ulrich

  • Publication date : 21 December 2020 More

    Liver stiffness by transient elastography to detect porto-sinusoidal vascular liver disease with portal hypertension Hepatology

    Autors : Elkrief Laure Marie Lazareth Sylvie Chevret Paradis Valérie Marta Magaz Lorraine Blaise Laura Rubbia-Brandt Moga Lucile Durand François Audrey Payancé Plessier Aurélie Cendrine Chaffaut Valla Dominique Marion Malphettes Alba Diaz Jean-Charles Nault Pierre Nahon Etienne Audureau Vlad Ratziu Castera Laurent Juan-Carlos Garcia Pagan Nathalie Ganne-Carrie Rautou Pierre-Emmanuel ANRS CO12 CirVir group

  • Publication date : 19 November 2020 More

    Iron chelation rescues hemolytic anemia and skin photosensitivity in congenital erythropoietic porphyria Blood

    Autors : Jean-Marc Blouin Cécile Ged Magalie Lalanne Isabelle Lamrissi-Garcia Fanny Morice-Picard Pierre Costet Daher Raed François Moreau-Gaudry Aurélie Bedel Puy Hervé Gouya Laurent Emmanuel Richard